Psychostimulant drugs like cocaine have been shown to have primary reinforcing effects that contribute to the initiation of drug-taking behavior. However, secondary or conditioned effects of psychostimulants may significantly promote the maintenance of drug use. That is, drug effects become associated with environmental stimuli that can then elicit drug-like effects and direct drug-seeking behavior even in the absence of the drug. Understanding the neurophysiological bases of these conditioned responses may be pivotal to understanding the mechanisms of craving and relapse than occur in former addicts even after long-term abstinence. The conditioned effects of drugs of abuse have been well characterized in animal behavioral studies and have been shown to induce craving in humans. Previous research on cocaine conditioning has provided intriguing but equivocal evidence that the conditioned effects of cocaine may be mediated in a qualitatively different way than its direct effects. This proposal will test hypotheses drawn from this evidence, namely that (1) dopamine receptors play a lesser role and (2) opioid receptors a greater role in mediating cocaine-induced conditioned versus direct effects. The locomotor stimulant effects of cocaine will be conditioned in rats by repeatedly airing cocaine administration with a distinct environment. Representative dopamine and opioid ligands will be tested for the capacity to disrupt the expression of conditioned locomotor stimulant effects. Additionally, the same drugs will be tested as antagonists of cocaine-induced locomotor stimulant effects. The research design uses protocols matched for effect size so that direct comparisons between the conditioned and direct stimulant effects of cocaine, and their modulation by drugs, can be made. Results from these studies will lay the foundation for more in depth studies on the neuropharmacology of the conditioned effects of cocaine. Present approaches to medications development for cocaine abuse typically screen for drugs that mimic and/or antagonize the direct effect of cocaine. However, these approaches have not been successful in developing a useful pharmacotherapy. If study of cocaine-induced conditioning delineates fundamentally different processes, characterization of its neuropharmacology will result in novel treatment strategies. Further, this methodology may well model a component of drug craving in animals. If results warrant such a link to be drawn, then the procedure would be a useful screen for anticraving medications.